Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

The role of modern imaging modalities on deep brain stimulation targeting for mental illness.

INTRODUCTION: The reversible nature of deep brain stimulation (DBS) brought renewed interest on surgery to medically intractable mental illnesses. The explosion of anatomical and functional imaging has allowed the development of new potential targets and the understanding of historical targets. METHODS: Fifteen patients undergoing stereotactic surgery for movement disorders, at UCLAs interventional MRI operating-room, were studied with fiber tracking. Stereotactic targets and fiber tracking were determined on MRIs using the Schaltenbrand-Wahren atlas for definition in the iPlan software. Cingulate, subcaudate, BA25/CgWM, amygdala, posterior hypothalamus, orbitofrontal cortex, nucleus accumbens, anterior limb of the internal capsule and dorsomedial thalamus were studied. DTI parameters used ranged from 10 to 20mm for voxel size in the x/y/z planes, fiber length was kept constant at 36 mm, and fractional anisotropy (FA) threshold varied from 0.20 to 0.25. RESULTS: Reliable interconnectivity of targets were determined with DTI and related to PET imaging. Mental illness targets were observed with functional and fiber tract maps. This confirmation yields reliability to DTI imaging in order to determine novel targets and enhance the understanding of areas not well understood. CONCLUSIONS: Currently available imaging techniques, the reversibility of DBS to modulate targets promises to bring a brighter future for surgery of mental illness.

Radiosurgery from the brain to the spine: 20 years experience.

INTRODUCTION: Radiosurgery evolved from brain to spine. Mechanical and computer advances in linear accelerator (LINAC) radiosurgery apply precise single/fractional stereotactic radiation to multiple pathologies. METHODS: During a 10-year span the senior author used proton-beam radiosurgery in over 300 lesions, followed by gamma-knife, adapted and dedicated LINACS, including cyber-knife, in another 700 patients. The last 10 years, experience was accumulated with the Novalis in over 3,000 patients. Novalis uses a beam-shaper in a high-speed delivery LINAC. It operates using conventional circular arc, conformal static beam, dynamic conformal or intensity modulated modes. Patients treated with Novalis at the UCLA since 1997 were evaluated regarding effectiveness, complications and failure. These results were compared with previous 1997 data. RESULTS: Over 4,000 patients with trigeminal neuralgia/intractable pain, arteriovenous malformations/angiomas, metastases, ependymomas, gliomas, meningiomas hemangiopericytomas, schwannomas, adenomas, hemangioblastomas, and chordoma were treated. Spinal lesions were treated with frameless stereotaxis and on-line precision checks. Treatment was expeditious, comfortable and with reduced complications. Success is similar or superior to published data. Reduced treatment time of complex lesions and highly homogeneous dose compares favorably to other radiosurgery. CONCLUSIONS: The senior author's experience validates the novel shaped-beam approach. Long-term follow-up supports safety and effectiveness and capability to treat brain and spine.

Stereotactic radiotherapy for the treatment of pituitary adenomas.

PURPOSE: The aim of this study was to retrospectively review local control and morbidity following stereotactic radiotherapy (SRT) for pituitary adenoma. METHODS: Between 1997 and 2004, 39 patients with pituitary adenomas received SRT. Median age was 56 years (range: 13 to 90 years). Thirty-three patients underwent incomplete transsphenoidal surgery prior to SRT and six had unresectable tumors. The largest tumor dimension varied from 1.7 to 6 cm (median: 3 cm). Tumor volume varied from 1.2 to 56 mL (median 10.5 mL). Thirty-five tumors were < or = 1 mm from the optic chiasm/nerve. Thirty-three tumors were non-functional. SRT was delivered by a dedicated linear accelerator (Novalis, Heimstetten, Germany). Beam collimation was achieved by a fixed circular collimator (five patients) or a micro-multileaf collimator (34 patients). Total dose varied from 4500 to 5040 cGy (median: 4860 cGy) and was prescribed at the 90 % isodose line. RESULTS: After a median follow-up of 32 months (range: 12 to 94 months), the local control rate was 100 %. Tumor size was stable in 26 patients and decreased in 13 patients. Hormone normalization did not occur following SRT. New endocrine deficiency occurred in six patients. No patient developed cranial nerve injury or second malignancy following treatment. CONCLUSIONS: SRT achieves a high rate of local control and a low rate of treatment-induced morbidity. SRT is applicable to pituitary adenomas in close proximity to the optic apparatus and tumors in excess of three centimeters in the greatest dimension. Further follow-up is necessary to establish the long-term outcome following SRT for pituitary adenomas.

Linear accelerator stereotactic radiosurgery for the treatment of gelastic seizures due to hypothalamic hamartoma.

PURPOSE: There are reports of successful gamma-knife stereotactic radiosurgery (SRS) for the treatment of gelastic seizures associated with a hypothalamic hamartoma. The authors reviewed the results of linear accelerator (LINAC) radiosurgery for patients with medically refractory gelastic seizures due to a sessile hypothalamic hamartoma. METHODS: Three patients with gelastic seizures received SRS between 2003 and 2004. All patients had associated partial complex and/or generalized seizures. One patient demonstrated aggressive behavior. Sessile hamartomas varying in diameter from 6 to 14 mm were identified by MRI. SRS was delivered to a single isocenter by a dedicated LINAC equipped with either a circular beam collimator or a micromultileaf collimator. Patients received 1500 to 1800 cGy prescribed at the 90 to 95 % isodose line. Seizure outcome was scored according to Engel's classification. RESULTS: Two patients became free of gelastic and partial complex/generalized seizures seven and nine months after radiosurgery. These patients remain free of seizures at 17 and 15 months, respectively, after treatment (Engle Class IA). One patient experienced a decline in gelastic seizure frequency nine months after treatment (Engle Class II) without significant reduction in aggressive behavior. Follow-up MRI demonstrated no change in the size or signal characteristics of any tumor. No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. CONCLUSIONS: LINAC SRS represents a safe and effective therapeutic alternative for patients with medically refractory gelastic seizures due to unresectable hypothalamic hamartomas. Radiosurgery is associated with a latency of several months from treatment to reduction in seizure frequency. Further follow-up is required to establish the duration of seizure control following radiosurgery.

The influence of food restriction during different periods of pregnancy.

Considering that the energy balance can be affected by factors such as pregnancy and food restriction and that the development of foetuses is different during different periods of pregnancy, the aim of this paper was to study the effects on the maternal and offspring energy balance of food restriction imposed at different periods of pregnancy. Pregnant and non-pregnant rats were subjected to four food intake treatments. Control groups received food ad libitum during the 20 days of the experiment. The other three groups were food restricted by receiving 50% of the control group food intake during the first half, the second half, or the whole experimental period. Food restriction imposed during the first half of the experimental period permitted a recuperation of energy intake, but compared to the control group, the rats gained less energy in the body. The offspring parameters studied were not affected by food restriction during the first half of the experimental period. Food restriction during the second half was more deleterious to the dams and to the offspring, which were born with less energy and weight. When food restriction was applied during the whole experimental period, the impairment in energy balance of offspring was similar to the one observed when food restriction occurred during the second half of pregnancy added to a decreased number of offspring. The dams, however, were more deeply affected than when food restriction was applied during the first half of the experimental period.